Gold(I)-Catalyzed Intramolecular [4+2] Cycloadditions

The intramolecular [4+2] cycloaddition of alkenyl- (1) and
aryl-substitued 1,6-enynes 2 was described by the group of Antonio
Echavarren from the Institute of Chemical Research of Catalonia (ICIQ), Spain, (J.
Am. Chem. Soc.2008, 130, 269.
). The transformations
proceed via catalysis involving cationic Au(I)-complexes and furnish bicyclic
products from 1 and tricyclic derivatives from 2. Heating under
microwave conditions leads to reduced reaction times (h vs. min) and improved
yields. Precatalyst 4 proved to be more
reactive than 3 especially under room
temperature conditions. Substrates 2 with m-substituents at the
aryl moiety gave mixtures of regioisomers, whereas other minor by-product
formation was observed via a 6-endo cyclization pathway.

One-Pot Three-Component Isoxazole Synthesis

The group of Thomas Müller from Heinrich-Heine-Universität Düsseldorf,
Germany, has developed the synthesis of 3,4,5-substituted isoxazoles via a
one-pot three-component reaction pathway (Synthesis2008, 293.
). In the first sequence, alkynones 1 are obtained by Sonogashira
coupling of acid chlorides with terminal alkynes at room temperature. After
addition of hydroximinoyl chlorides 2 and Et3N
to the same reaction vessel, alkynones 1 reacted further to the
corresponding isoxazoles via a 1,3-dipolar cycloaddition with in situ
generated aromatic nitrile oxides from 2. By
employing microwave heating for the cycloaddition step, reaction times could be
reduced from three days to 30 min, while increased yields of the final products
and less by-product formation (dimerization of nitrile oxides to furoxan oxides)
were observed.

Synthesis of Substituted 2-Aminoimidazoles

The synthesis of mono- and disubstituted 2-aminoimidazoles by the reaction of
diverse α-haloketones with N-acetylguanidine was reported by Yulin Lam and
co-workers from the National University of Singapore (J. Comb. Chem.2008,
10, 118.
). In the first reaction step, the corresponding imidazol-2-acetamides
were obtained in excellent yields. Further deacylation with H2SO4 and MeOH/H2O
(1:1) or EtOH, respectively, and subsequent formation of the free amine with 5 M
KOH in MeOH furnished the 2-aminoimidazole products, again in high yields. The
overall reaction time could be cut down to only 20 min compared to several days
under conventional room temperature conditions.

Suzuki-Miyaura Coupling/Aldol Condensation Cascade Reaction

Jung-Nyoung Heo and co-workers from the Korea Research Institute of Chemical
Technology have disclosed a cascade reaction of o-substituted aryl halides and
o-formyl or o-acetyl-arylboronic acids - involving first a Suzuki-Miyaura
coupling and a subsequent intramolecular aldol condensation - for the synthesis
of phenanthrene derivatives (J. Org. Chem.2008, 73, 495.
). Crucial for
obtaining the phenanthrenes in high yields is the ratio of the solvent mixture,
with toluene/EtOH 2:1 leading to optimum results. When a ketone is employed as
aldol acceptor (R4 = Me) DavePhos as ligand has to be used, and a lower
temperature of 120 °C for 5 min for the Suzuki coupling was necessary followed
by an additional 10 min at 150 °C for the aldol condensation. The same is true
for some aryl halide building blocks (R1 = CO2Et, CN; X = Cl), where either
DavePhos or SPhos has to be applied in order to prevent side reactions and to
receive the phenanthrene products in good yields. The reversed approach was
possible as well where boronate esters are reacted with 2-bromoaryl
carboxaldehydes.